title: Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and meta-analysis.
abstract: BACKGROUND
  In the past decade, more than 200 cases of nephrogenic systemic fibrosis (NSF) have been identified, primarily among patients with advanced kidney disease. Multiple studies have suggested an association between gadolinium-based contrast agents (GBCAs) and NSF. We performed a systematic review and meta-analysis to examine this potential association.
  
  
  METHODS
  A systematic review of studies examining the association between any GBCA and NSF was performed. A search for controlled studies was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. If controlled data for a GBCA was not available, we searched for case reports and series. Relevant data were extracted and meta-analyses were performed.
  
  
  RESULTS
  Seven of 144 identified studies met inclusion criteria; gadodiamide was the sole or predominant GBCA in four of these; one study exclusively examined gadopentetate. Other GBCAs were not specifically examined in controlled or uncontrolled studies. Meta-analysis of controlled trials demonstrated a significant association between GBCA exposure and NSF [odds ratio (OR) 26.7; 95% confidence interval (CI) 10.3-69.4] and gadodiamide and NSF (OR 20.0; 95% CI 3.7-107.8). Examination of the evidence using established criteria suggested that this association was causal.
  
  
  CONCLUSIONS
  The current state of evidence suggests an association and potentially causal link between the use of GBCAs and the development of NSF among patients with advanced kidney disease. Additional study is warranted to clarify the potential association of GBCAs other than gadodiamide with NSF.
authors.affiliation: 1Center for Evidence-Based Practice, University of Pennsylvania Health System, Philadelphia, PA 19104, USA. rajender.agarwal@uphs.upenn.edu
authors.forename: Rajender
authors.initials: R
authors.lastname: Agarwal
authors.forename: Steven M
authors.initials: SM
authors.lastname: Brunelli
authors.forename: Kendal
authors.initials: K
authors.lastname: Williams
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Craig A
authors.initials: CA
authors.lastname: Umscheid
mesh_terms: D003287:Contrast Media / Q000009:adverse effects*; D005682:Gadolinium / Q000009:adverse effects*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced*; D009942:Organometallic Compounds / Q000009:adverse effects*; D006435:Renal Dialysis
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium